7-78630386-T-C

Position:

• chr7-78630386-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000354212.9(MAGI2):​c.419-3147A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 148,668 control chromosomes in the GnomAD database, including 30,151 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (30151 hom., cov: 26)
• Consequence: MAGI2 ENST00000354212.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.613

Genes affected

MAGI2 (HGNC:18957): (membrane associated guanylate kinase, WW and PDZ domain containing 2) The protein encoded by this gene interacts with atrophin-1. Atrophin-1 contains a polyglutamine repeat, expansion of which is responsible for dentatorubral and pallidoluysian atrophy. This encoded protein is characterized by two WW domains, a guanylate kinase-like domain, and multiple PDZ domains. It has structural similarity to the membrane-associated guanylate kinase homologue (MAGUK) family. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.419-3147A>G		intron_variant		ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.419-3147A>G		intron_variant		1	NM_012301.4	ENSP00000346151	P4

Frequencies

GnomAD3 genomes AF: 0.632 AC: 93836 AN: 148570 Hom.: 30131 Cov.: 26

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.597

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.625

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.632 AC: 93906 AN: 148668 Hom.: 30151 Cov.: 26 AF XY: 0.634 AC XY: 45721 AN XY: 72092

Gnomad4 AFR AF: 0.528

Gnomad4 AMR AF: 0.668

Gnomad4 ASJ AF: 0.738

Gnomad4 EAS AF: 0.859

Gnomad4 SAS AF: 0.646

Gnomad4 FIN AF: 0.685

Gnomad4 NFE AF: 0.655

Gnomad4 OTH AF: 0.628

Alfa AF: 0.646 Hom.: 39684

Bravo AF: 0.631

Asia WGS AF: 0.755 AC: 2624 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs38121; hg19: chr7-78259702; COSMIC: COSV62679155; COSMIC: COSV62679155;